LEXINGTON, Mass.—Takeda Pharmaceuticals’ Budesonide Oral Suspension (BOS), the company’s investigational therapy for the treatment of eosinophilic esophagitis (EoE), has achieved co-primary and key secondary efficacy outcomes with statistical significance compared to placebo, in the first of two pivotal Phase 3 studies. BOS is an investigational, novel mucoadherent topical corticosteroid formulation being evaluated for the treatment of EoE in adolescents and adults.

Positive results on clinical endpoints were presented from a randomized, double-blind, placebo-controlled trial that investigated the safety and efficacy of BOS over 12 weeks of treatment among adolescent and adult patients aged 11 to 55. Results on histologic, symptomatic and endoscopic endpoints were presented today at the 2019 American College of Gastroenterology Annual Scientific Meeting (Oct 25-30, San Antonio, TX).

“I am very much looking forward to presenting positive results on the clinical endpoints of this Phase 3 trial of Budesonide Oral Suspension, the first U.S. Phase 3 study in patients with EoE to assess histologic, dysphagia, and endoscopic response to a medical treatment,” said Ikuo Hirano, M.D., professor of Medicine, Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine. “Patients with EoE have long suffered with dysphagia and esophageal inflammation in the absence of an FDA-approved treatment. The results from this Phase 3 study of a medication specifically designed for esophageal delivery in EoE are promising in addressing an unmet need in the management of EoE.”

EoE is a rare, chronic immune-mediated disease of the esophagus that occurs when eosinophils accumulate in the esophagus, resulting in inflammation. Children, adolescents and adults with EoE can experience difficulty eating and/or swallowing, potentially resulting in discomfort and pain. EoE that is uncontrolled can lead to esophageal remodeling and fibrosis, resulting in dysmotility and/or food impaction.

Currently there are no FDA-approved therapeutic options specifically indicated for the treatment of EoE. Guidelines for EoE recommend the elimination of targeted food from patient diets, the use of proton pump inhibitors, and/or treatment with topical corticosteroid formulations.

In this clinical study, patients aged 11 to 55 years with EoE and dysphagia were randomized 2:1 to receive 2.0 mg BOS or placebo twice daily for 12 weeks. Following a placebo lead-in period of up to six weeks, a total of 318 patients received at least one dose of double-blind therapy (BOS, n=213; placebo, n=105). The co-primary efficacy endpoints of this study were histologic response and dysphagia symptom response after an initial 12 weeks of therapy.

Histologic response was measured as having a peak eosinophil count less than or equal to six eosinophils per high-powered field, and dysphagia symptom response was measured as a greater than or equal to 30% reduction from baseline to final treatment as assessed by the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measurement tool.

The key secondary efficacy endpoint included change in DSQ score from baseline to final treatment. The change in EoE Endoscopic Reference Score (EREFS) from baseline to final treatment period was evaluated as a secondary endpoint. Study results found significantly more histologic responders and dysphagia symptom responders in the BOS-treated group versus the placebo-treated group (53.1% vs 1.0%, P< .001; 52.6% vs 39.1%, P=.024, respectively). Improvements in mean DSQ score from baseline to week 12 were also significantly greater in the BOS group (n=197) than the placebo group (n=89) (−13.0 vs −9.1; P=.015). Similarly, improvements in mean EREFS scores were significantly greater with BOS (n=202) than placebo (n=93) (−4.0 vs −2.2; P< .001).

The trial also evaluated the safety of BOS, including measuring the number and types of adverse events. The majority of treatment-emergent adverse events (TEAEs) were mild to moderate in severity, and similar between the BOS- and placebo-treated groups. This is the first of two pivotal Phase 3 studies; the findings presented during ACG reflect aggregate data because the second Phase 3 double-blind, placebo-controlled maintenance study is ongoing.

In total, 61.0 percent (194/318) of patients reported a TEAE (BOS, 61.0% [130/213]; placebo, 61.0% [64/105]), with 2.5 percent of patients experiencing a TEAE leading to dose discontinuation (BOS, 1.4%; placebo, 4.8%). TEAEs that affected 2 percent or more of the patients in either the placebo or BOS arm of the study included nasopharyngitis, sinusitis, esophageal candidiasis, oral candidiasis and upper respiratory tract infection. TEAEs of candidiasis such as oral or esophageal candidiasis were seen in fewer than 5 percent of patients overall and in either treatment group. Rates of individual TEAEs such as oral candidiasis cannot yet be disclosed by treatment group until the maintenance study completes. There were no life-threatening TEAEs or deaths reported.

“We are deeply committed to bringing EoE-specific clinical evidence to patients and providers, and driving further awareness to the needs of this community. We consider the results of this scientifically rigorous study an important step toward a more data-driven treatment approach for patients with EoE. We are focused on the continued investigation of BOS as a potential treatment option for this community and look forward to sharing further study data,” noted Debra Silberg, M.D., Ph.D., FACG, vice president, clinical science head GI, Takeda.

The complete abstract, as well as three additional Takeda-sponsored EoE-related abstracts being presented during ACG, can be accessed here.